Immunogenicity of DNA vaccines expressing human immunodeficiency virus type 1 envelope glycoprotein with and without deletions in the V1/2 and V3 regions.
DNA vaccines that express the human immunodeficiency virus type 1 HXB-2 envelope glycoprotein (Env) with or without deletions of the major variable regions V1/V2 and V3 were tested for the ability to raise enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody in New Zealand White (NZW) rabbits. Three forms of the Envs were examined: gp120, the surface (SU) receptor-binding domain; gp140, the entire extracellular domain of Env; and gp160, the complete form of Env. For the forms of Env containing the variable regions, the gp120-expressing DNA plasmid was more immunogenic than the gp140- or gp160-expressing DNA plasmids. Removing the V1/2 and V3 variable regions increased the immunogenicity of the gp140- and gp160-expressing DNAs. Deletion of the variable regions also resulted in antibody responses against determinants that were not presented by the forms of Env containing the variable regions. Despite the improved immunogenicity, removing the V1/V2 and V3 domains did not improve the ability of Env to raise neutralizing antibodies. These results suggest that increasing the exposure of internal structures of Env that include the CD4-binding site does not necessarily result in the generation of better neutralizing antibody.
Lu
S
S
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Wyatt
R
R
Richmond
J F
JF
Mustafa
F
F
Wang
S
S
Weng
J
J
Montefiori
D C
DC
Sodroski
J
J
Robinson
H L
HL
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019556:COS Cells; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059761:HIV envelope protein gp120 (135-148); C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1